Physiology & Behavior, Vol. 59, No. 6, I I I I-1 115.

1996
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The Effects of Chronic Corticosterone on Memory

Performance in the Platform Maze Task
MARK E. BARDGE’IT,*t’ JOHN W. NEWCOMER* AND GEORGE T. TAYLOR?

“Deparhnent of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110-1093 USA and I-laboratory
for Psychobiology, Department of Psychology, University of Missouri-St. Louis, St. Louis, MO 63121 USA

Received 8 May 1995

BARDGETT, M. E., J. W. NEWCOMER AND G. T. TAYLOR. The effecrs of chronic corticosterone on memory
performance in the plarform maze task. PHYSIOL BEHAV 59(6) 111 l- 1I 15, 1996.-Acquisition and reversal of a
memory task dependent on hippocampal integrity were assessed in rats following chronic corticosterone treatment.
Young adult male rats were injected daily with corticosterone (10 mg/kg, SC) for 8 weeks. Memory was assessed
during the last week of treatment with an elevated platform maze. During acquisition trials, corticosterone-treated rats
did not differ from vehicle-treated controls in either the location of first hole chosen nor in the latency to locate the
escape hole. In the reversal trials, when the position of the escape hole was rotated 135”, both groups successfully
reversed their responses without persevering towards the previously rewarded escape hole location. These findings
suggest that, despite the probability of corticosterone-induced changes in hippocampal physiology, chronic corticos-
terone treatment does not adversely affect performance in a memory task dependent on hippocampal integrity.

Glucocorticoid Glucocorticoid receptors Hippocampus Memory Learning Aging

Stress

RECENT research has revealed the deleterious effects of exces-
sive or prolonged glucocorticoid treatment on hippocampal neu-
rons, including reduced glucocorticoid binding, inhibition of glu-
cose uptake, dendritic involution, and neuronal loss (10,22,27).
Given the hippocampal role in learning and memory (16,24),
behavioral studies have begun to address the potential cognitive
consequences of glucocorticoid-induced hippocampal deficits.
Several human and animal studies have demonstrated impaired
task that is sensitive to hippocampal disruption (2,13,14,18).
Young adult male rats were injected daily with either corticos-
terone (10 mg/kg, SC) or vehicle (peanut oil) for 8 weeks. We
have shown that this dose of corticosterone produces a fourfold
elevation of plasma corticosterone (1). During the last week of
treatment, all animals were tested in the elevated platform maze.
METHOD

performance in tasks dependent on hippocampal function after

glucocorticoid treatment (3-$15). However, not all memory
tasks associated with hippocampal integrity are adversely af-
fected by prolonged exposure to glucocorticoids (12,26).
We have recently shown that a 2-month regimen of corticos-
terone, the endogenous glucocorticoid of the rat, impairs sponta-
neous alternation behavior in rats without producing overt hip-
pocampal cell loss (1). Although spontaneous alternation is sensi-
tive to hippocampal disruption (2,201, the question remains as to
whether this corticosterone-induced impairment generalizes to
other memory tasks dependent on hippocampal function. To
answer this question, we examined the performance of corticos-
terone-treated and control rats in the elevated platform maze, a
Corticosterone Treatment
Young adult (80- 100 days old) male Long-Evans rats (n = 13
per group; Charles River) were used in the experiment. Animals
were housed individually in hanging wire cages with food and
water available ad lib throughout the experiment. Lighting was
on a 12-h light/ 12-h dark cycle, and room temperature (20-22°C)
and relative humidity (55 f 5%) were controlled automatically.
Animals were injected SC with the peanut oil vehicle or corticos-
terone (10 mg/kg body weight; Sigma, St. Louis, MO), which
increases plasma corticosterone levels fourfold 1 h after treatment
(1). Injections were administered daily for 56 days during the
first half of the dark cycle. Housing and experimental procedures

’Requests for reprints should be addressed to Mark E. Bardgett, Department of Psychiatry, Washington University School of Medicine, Box 8134,
4940 Children’s Place, St. Louis, MO 63110.

1111
1112
were performed according to the current Guide for the Care and
Use of Laboratory Animals (USPHS) under protocols approved
by the Interdisciplinary Animal Care and Use Committee at the
University of Missouri-St. Louis.
Elevated Plarfom Maze
The elevated platform maze test was conducted during the last
week of treatment. The apparatus (Fig. 1) was similar to the one
originally described by Barnes (2). It consisted of a white,
circular platform (1.2 m in diameter) with 18 equally spaced,
9-cm holes located along the perimeter of the platform. A clear
piece of Plexiglas measuring 10 cm high X 30 cm long X 1 cm
thick was located between each hole. A black escape tunnel was
located beneath one hole (the escape hole). The platform could be
rotated without moving the escape tunnel from its fixed position.
The platform was rotated in a randomized manner from trial to
trial to disrupt the use of odor trails in locating the escape hole.
The platform was brightly lit by two 150-W spotlights positioned
directly above the maze. A trial started by placing a rat, at a
random orientation, into a cylindrical start chamber with a false
bottom. The chamber was located in the center of the platform
and was raised to the ceiling by a pulley located in an adjacent
room.
Each rat was given two trials per day over I consecutive days.
Trials were monitored on a closed-circuit television located in an
adjacent room. On the first of day of testing, a rat was placed in
the escape tunnel for a 4-min adaptation period and returned to
its home cage for 20 min, after which the first trial started. Two
scores were obtained for each trial: 1) first error-defined as the
number of holes between the location of initial hole investigated
and the escape hole, and 2) latency to enter-defined as the time
(in seconds) elapsed between the start of the trial and the rat
entering the escape hole. The first error was recorded when the
rat’s nose dropped below the maze surface into an incorrect hole.
After entering the escape tunnel, the rat was allowed to remain
there for 1 min. If the rat did not enter the escape tunnel within
PIG. 1. Schematic drawing of elevated platform maze. Eighteen holes
surroundedthe perimeterof the tabletop and each hole was separatedby a
small Plexiglas wall, one of which is shown on the top left side of the
table. The cylindrical start container located in the middle of the tabletop
was raised at the beginning of each trial. The table top could be rotated
after each trial. Trials were terminated when the rat entered the escape
hole and went into the escape tunnel (shown extending from the lower
left side of the table), which was closed during each trial.
BARDGE’IT, NEWCOMER AND TAYLOR
240 s, it was placed in the tunnel for 1 min. Twenty minutes after
the end of the first trial, the second trial started. On subsequent
days, each rat received two trials separated by a 20-min intertrial
interval. Between trials, rats were returned to their home cage,
and the escape tunnel box was washed with a 50% alcohol
solution. Testing was conducted during the first half of the dark
cycle.
Throughout the first nine trials (acquisition trials), the escape
tunnel position was fixed in a particular location in the testing
room. On the 10th trial, the escape tunnel location was rotated
135”, and remained in this new location for the last five trials
(reversal trials). On these latter trials, perseveration for the
previous escape tunnel location was measured and defined as the
number of holes between the first hole investigated and the
former escape hole location.
Data Analysis
Separate analyses were conducted for the acquisition and
reversal phases of testing. In each analyses, the first error, latency
to enter, and perseveration (reversal phase only) scores were
compared between groups across trials by a two-way, repeated-
measures ANOVA. The main factors were treatment (between
subjects) and trial (within subjects). A Mann-Whitney test was
used to compare groups at each trial on the first error, latency to
enter, and perseveration measures. Significant differences be-
tween groups were accepted for alpha levels < 0.05.
RESULTS
First Error
Across acquisition trials, there were no significant differences
between corticosterone- and vehicle-treated rats on the first error
measure (Fig. 2). The reduction in first error was significant
across acquisition trials [trial effect: F(8, 192) = 5.3, p < O.OOOl].
In the initial trial following reversal of the escape hole
location, there was significant increase in the first error [Mann-
Whitney test: ~(26) = 3.5, p < O.OOOS]in both the corticos-
terone-treated and vehicle groups. Across the remaining reversal
trials, there was a significant reduction in first error [trial effect:
F(4, 96) = 6.6, p < O.OOOl]and a significant interaction between
corticosterone treatment and time [treatment X time interaction:
F(4, 96) = 2.5, p < 0.051. Corticosterone-treated rats displayed a
significantly lower first error score on trial 11 relative to vehicle-
treated rats [Mann-Whitney: ~(13) = 2.3, p < 0.021. There were
no other significant, between-group differences over the remain-
ing reversal trials.
Latency to Enter
There was a significant decrease in the latency to enter the
escape hole over acquisition trials [trial effect: F(8, 192) = 11.8,
p < O.OOOl].There were no significant differences between corti-
costerone- and vehicle-treated rats across acquisition trials (Fig.
3), although there was a trend toward reduced latency at trial 5 in
~~~rticosterone-treated rats [Mann-Whitney: ~(13) = 1.7, p =
. .
Latency to enter was initially increased after reversal of the
escape hole [Mann-Whitney: ~(26) = 4.2, p < O.OOOl], which
was followed by a significant decrease across the remaining
reversal trials [trial effect: F(4, 96) = 8.7, p < 0.00011. There
were no significant, between-group differences in any of the
reversal trials.
CHRONIC CORTICOSTERONE AND MEMORY 1113

o!.,.,.,.,.!.,.,,
0 2 4 6 8 10 12 14

Trial

FIG. 2. Effects of 8-week corticostemne treatment (10 mg/kg) on first error measure. The scores denote the mean number of holes between the initial
hole investigated and the escape hole ( f SEM; n = 13 per group). Arrow at trial 10 indicates first reversal trial. Significant difference between groups at
trial 11 denoted by asterisk ( p < 0.02).

Perseveration (Fig. 4). There was a statistical trend towards an interaction

Perseveration in choosing the original escape hole location
was measured during the reversal trials. It was expected that
during the initial reversal trials, animals would make the original
escape hole location their first choice. Then across the remaining
trials, the animals would make the new escape hole location their
first choice. A deficit in this transition of initial hole choice could
be interpreted as an error of perseveration. To address this
possibility, we determined the proximity of the first hole chosen
on each reversal trial to the prior escape hole location.
Perseveration for the prior escape hole location decreased
significantly over reversal trials [trial effect: F(4, 96) = 6.7,
p < O.OOOl],as indicated by the increased distance between the
first hole chosen and the prior escape hole location across trials
[treatment X trial interaction: F(4, 96) = 6.7, p = 0.061, which
indicated increased perseveration in the corticosterone rats on
trial 14, t(24) = 2.0, p = 0.06.
DISCUSSION
Prolonged elevation of plasma glucocorticoids exerts a pro-
found influence on hippocampal physiology (22) and several
behaviors dependent on hippocampal integrity (3-5,151. We have
recently shown that a 2-month regimen of daily corticosterone
administration impairs spontaneous alternation behavior in the rat
(1). However, using an identical treatment regimen, the present
study demonstrates that chronic corticosterone does not impair
performance in the elevated platform maze task, another memory

0-I . , . , . ( . , . ! . , . , ,
0 2 4 8 8 10 12 14

Trial

FIG. 3. Effects of 8-week corticostercne treatment (10 mg/kg) on latency measure. The scores denote the mean latency (in seconds) between the start of
the trial and the rat entering the escape hole (f SEM; n = 13 per group). Arrow at trial 10 indicates frost reversal trial. There were no significant
differences between tbe groups at any trial.
1114
paradigm sensitive to hippocampal perturbation (2,13,14,18). This
finding suggests that not every behavior associated with hip-
pocampal function is adversely affected by prolonged exposure to
glucocorticoids.
We chose to assess the effects of chronic corticosterone
treatment on performance in the elevated platform maze because
of its putative sensitivity to hippocampal deficits (2,13,14,18).
Barnes (2) had earlier demonstrated that impaired performance in
the elevated platform task could be linked to deficits in hip-
pocampal long-term potentiation (LTP), which can be disrupted
by corticosterone (3,8,17). We also chose the elevated platform
task because it does not rely on food deprivation or aversive
stimuli, which could have confounded physiological stress with
the corticosterone treatment. Specifically, a food-motivated mem-
ory task was avoided, because food deprivation can increase
circulating corticosterone levels (7,21,25). In addition, a shock-
motivated memory task may have been confounded by the inter-
action of glucocorticoids with pain sensitivity (19). Despite the
moderate level of reinforcement provided by the darkened escape
hole in the elevated platform task, robust learning was demon-
strated on all of the measures across acquisition and reversal
trials.
Regardless of its potential effects on hippocampal physiology,
chronic corticosterone treatment did not significantly alter mem-
ory performance in the elevated platform maze. Several factors,
such as dose, age, or rat strain, could account for this finding. It
is conceivable that a higher, supraphysiological dose or a longer
treatment duration could have impaired performance; however,
the dose was chosen to produce stress-like levels of plasma
corticosterone (l), and the treatment duration was chosen to
maximize the effects of corticosterone without producing mortal-
ity, as previously reported with longer treatment durations (23).
Although younger or older rats may be more susceptible to
corticosterone-induced behavioral impairments (6,l l), behavioral
deficits have been observed in young adult rats after prolonged
corticosterone treatment (1,s). The Long-Evans rats used in the
present study may be less sensitive to chronic corticosterone
relative to other strains; however, Luine et al. (12) have reported
that chronic corticosterone does not alter spatial memory in
Fisher-344 rats, which are more sensitive to corticosterone-in-
O-
. - tgiccesterone
a-
I-
?!
6-
i * T
00 9 10 11
Trial
FIG. 4. Effects of g-week corticosterone treatment (10 mg/kg) on perseverationmeasure. The scores denote the mean number of holes between the
initial hole investigated and the escape hole location during the acquisition phase of testing ( f SEM; n = 13 per group). Higher scores indicate less
perseveration.There were no significant differences between the groups at any trial.
BARDGETT, NEWCOMER AND TAYLOR
duced hippocampal neuronal loss (23). Thus, the above factors
could have mitigated against corticosterone-induced deficits in
the elevated platform maze task, but may not fully account for
this finding.
The results from this study may simply indicate that the type
of memory involved in the elevated platform maze task may have
been spared after prolonged glucocorticoid treatment, relative to
the impairments observed in other memory paradigms after simi-
lar treatment. Differences in the temporal characteristics of the
elevated platform maze task vs. other paradigms may explain
why corticosterone treatment did not disrupt performance in the
elevated platform maze. For example, performance in the sponta-
neous alternation task, which is impaired during chronic corticos-
terone treatment (11, depends on the short-term “retention” of
the previously chosen goal arm. Additionally, the location of the
goal arm in this task depends on the animal’s prior choice and,
thus, varies across trials. In contrast, performance in the elevated
platform maze depends on the long-term retention of the escape
hole location, which remains fixed across trials. Although rever-
sal of the escape hole location changes the fixed location, the
new escape hole location remains permanent over the remaining
reversal trials. Thus, given the adverse effects of glucocorticoids
on spontaneous alternation behavior, but not on performance in
the elevated platform maze, it is conceivable that glucocorticoids
have a greater effect on short-term, fluid memory than on long-
term, permanent memory.
The possibility that glucocorticoids could disrupt short-term
memory without affecting long-term memory is indirectly sup-
ported by electrophysiological studies. Filipini et al. (9) reported
that corticosterone treatment depressed LTP for the first 15-30
min after tetanic stimulation; however, LTP is similar to control
levels thereafter. This finding suggests that glucocorticoids can
compromise short-term memory retention, but does not produce a
long-lasting effect. Interestingly, the role of the hippocampus in
the elevated platform maze task may be limited to short-term
memory retention. Poucet et al. (18) found that hippocampal
inactivation impairs reversal learning in the elevated platform
maze when the intertrial interval is short (1 min), but has no
effect at longer intervals (24 h). These findings and the results
from our studies indicate that further investigations of hippocam-
12 13 14 16
CHRONIC CORTICOSTERONE AND MEMORY
pal-dependent memory after glucocorticoid treatment will need to
carefully consider the type of task studied and the timing of the
measures.
In summary, we have shown that memory performance in the
elevated platform maze is not altered after chronic corticosterone
treatment. This finding is important because it demonstrates that
not all behaviors associated with hippocampal function are ad-
versely affected by glucocorticoids. Thus, whereas the excessive
release of plasma glucocorticoids, which accompanies chronic
stress, aging, or hippocampal damage, may undermine specific
components of cognitive functioning, other aspects of memory
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Supported by a Dissertation Research Award from the American
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